1. Field of the Invention
The present invention relates to sunscreen compositions and methods for protecting the skin from ultraviolet radiation.
2. Description of the Prior Art
Sunscreens are used in the prevention of sunburns. Acute cutaneous responses to ultraviolet light (UVL) range from sunburn and suntan to photosensitivity states. The ultraviolet spectrum at the earth's surface consists of wavelengths from 290 nm to 400 nm. Normal sunburn and subsequent tanning result from UVB radiation (290 to 320 nm); UVA or long ultraviolet rays (320 to 400 nm) causes immediate pigment darkening but in high enough doses can induce new pigment formation. UVA is also responsible for most photosensitivity reactions. UVC (less than 290 nm) is not found at the earth's surface, it is filtered out by the atmosphere.
There is strong evidence that UVB is the major cause of aging of the skin and the development of cutaneous carcinoma. Evidence has been presented linking UVL exposure with skin cancer.
The most widely used chemical sunscreening agents are chemicals that protect the skin by absorbing UVL, and then dissipating the energy in a harmless manner. These compounds must (1) filter UVL between 290 and 320 m; (2) be stable; (3) be non-toxic; (4) be non-sensitizing; and (5) be non-volatile.
The major chemical sunscreens in use today are para-aminobenzoic acid derivatives, cinnamates, anthranilates, and benzophenones. (The previous discussion is essentially adopted from "Topical Photoprotective Agents", Algra, R. J. et al, International Journal of Dermatology, 17:628-634 (1978)).
Although these chemical agents are in wide use, most of them exhibit unwanted side problems. p-aminobenzoic acid for example may stain clothing yellow, especially after its exposure to the sun. Furthermore, allergic contact and photocontact dermatitis to p-aminobenzoic acid and its derivatives have been reported. Patients allergic to benzocaine, procaine, para phenylenediamine and sulfonylamide may have allergic reactions to p-aminobenzoic acid. A patient allergic to thiazide or sulfa drugs may have a reaction to sunscreens containing p-aminobenzoic acid or p-aminobenzoic acid esters. Contact dermatitis also occasionally develops from benzophenones and cinnamates; glyceryl p-aminobenzoic acid seems to be the most common cause. A number of other sunscreens can also cause photocontact dermatitis.
In view of these problems, it would be desirable to use compounds with somewhat decreased side effects. Especially desirable would be compounds belonging to a naturally occurring series, such as steroids.
The use of steroids in sunscreening compositions has been disclosed, mainly as anti-inflammatory additives. (See Algra et al supra, at page 631). Unfortunately, corticosteroids have little effect on sunburn erythema. Although both hydrocortisone and beta methasone-valerate may delay the onset of erythema at one to times the minimal erythema dose, neither is effective with higher doses of ultraviolet light.
Diassi, U.S. Pat. No. 3,542,811 describes 6-halo-6-dehydro-A-norprogesterones as useful for sunscreening. Pike, J. E. et al, U.S. Pat. No. 3,436,388 describe steroid 16-oxopregnan-21-oic acid di substituted amides, suggesting that when used topically they absorb a portion of erythema producing ultraviolet rays, and would thus be useful as ultraviolet screening agents. Pike, U.S. Pat. No. 3,178,459 describes androstano-(16,17-1',2')-benzenes, suggesting that they can be employed effectively as sunburn screens. Pike, U.S. Pat. No. 3,162,631 describes steroid 16.beta.-hydroxy-21-carboxylic acid .gamma.-lactones of the pregnane series, and also suggests that they can be used as ultraviolet screens. Diassi et al U.S. Pat. No. 3,488,733 describes the production of 14.alpha.- and 15.beta.-oxygenated-16-dehydro steroids of the pregnane series, suggesting that they could be used as sunscreening agents. Finally, Jackson et al U.S. Pat. No. 3,114,757 describes 6-fluorosteroids, also stating that they would be useful as sunscreening agents. None of the steroids described in these references however is a .DELTA..sup.5,7 steroidal diene or .DELTA..sup.3,5,7 steroidal triene.
Leigh, U.S. Pat. No. 3,981,996 describes sunscreening preparations comprising mixtures of vitamins A and D. It should be noted, of course, that vitamin D can be produced from provitamin D (a .DELTA..sup.5,7 steroidal diene) by a sequence of photochemical and thermal isomerization steps.
In addition, Holick, M. F., et al The New England Journal of Medicine, 303:349-354 (1980), have suggested the topical application of 1.alpha.,25-dihydroxy-7-dehydrocholesterol as being useful to deliver equivalent doses of 1.alpha.,25-dihydroxyvitamin D.sub.3 to patients with impaired vitamin D metabolism. The concept of applying hydroxylated provitamin D's (such as 1,25 dihydroxy-7-dehydrocholesterol) has been incorporated into U.S. Application Serial No. 022,393 filed Mar. 21, 1979 by Holick et al. Furthermore, the concept of adding to opacifying agents nonhydroxylated .DELTA..sup.5,7 steroidal dienes which are precursors of biologically active vitamin D has been incorporated into U.S. Application Ser. No. 193,297, filed Oct. 2, 1980 at the U.S. Patent Office, by Holick. Both of these applications however, relate to the use of precursors of biologically active vitamin D's.
A need therefore continues to exist for sunscreening compositions containing as the active sunscreening agent per se, molecules belonging to a family of naturally occurring compounds such as the steroids.